HLX43 for Advanced non-small cell lung cancer

Inclusion criteria

• {"criterion_text":"-Have a full understanding of the study content, process, and possible adverse reactions before the study, and sign the informed consent form (ICF); voluntarily participate in the study; be able to complete the study as per protocol requirements"}
• {"criterion_text":"-Male and female subjects with child-bearing potential must agree to use at least one highly effective contraception method during the study and within at least 8 months after the last dose of the investigational product; female subjects of childbearing age must be negative for pregnancy test within 7 days prior to enrollment."}
• {"criterion_text":"-Aged ≥ 18 years at the time of signing the ICF, male or female"}
• {"criterion_text":"-Histologically or cytologically confirmed, locally advanced (stage IIIB/IIIC) or metastatic (stage IV) NSCLC not suitable for radical treatment (complete surgical resection, concurrent/sequential radio-chemotherapy) according to the Union for International Cancer Control and the American Joint Committee on Cancer (AJCC) TNM staging system (8th edition), and should meet the following criteria: 1) Subjects without actionable genomic alterations (AGAs): • Subjects with non-squamous NSCLC must have documented negative test results for EGFR and ALK alterations. If no prior test results for EGFR and ALK are available, subjects must undergo EGFR and ALK testing at the study site. For subjects with squamous NSCLC, EGFR and/or ALK testing is not required prior to enrollment if their status is unknown; • No other known actionable genomic alterations, such as ROS1, NTRK, BRAF, MET exon 14 skipping, and RET; • Prior standard treatment failure of ≥ 1 line, including at least anti-PD-(L)1 antibody and platinum-based chemotherapy; 2) Subjects with AGAs: • Previous test results confirming the presence of one or more actionable genomic alterations; • Prior standard treatment failure of ≥ 1 line, including at least targeted therapy for driver gene alterations (patients with EGFR mutations must be previously treated with EGFR inhibitors) and platinum-based chemotherapy; Note: Definition of prior treatment failure with platinum-based chemotherapy: 1) Progressive disease following platinum-based chemotherapy in the recurrent or metastatic setting; 2) Progressive disease or recurrence during platinum-based chemotherapy, or within 6 months after the end of platinum-based chemotherapy during neoadjuvant chemotherapy, concurrent chemoradiotherapy, or adjuvant chemotherapy; 3) Intolerance to platinum-based chemotherapy"}
• {"criterion_text":"-At least one measurable lesion as per RECIST 1.1 within 4 weeks prior to randomization; Note: Measurable target lesions should not be selected from previous radiotherapy sites or brain lesions. A measurable lesion within the field of local radiotherapy can be selected as the target lesion only when it is the only optional target lesion and the imaging evidence before and after progression should be available"}
• {"criterion_text":"-Subjects who agree to provide archived tumor tissue specimens that meets the testing requirements (either from the most recent surgery or biopsy, preferably within 2 years) or agree to undergo a biopsy to collect tumor tissue for PD-L1 expression testing; Note: Formalin-fixed paraffin-embedded (FFPE) tumor samples (paraffin blocks or unstained sections, which must meet the quality control criteria for testing) collected from non-radiotherapy sites during the most recent surgery or biopsy at or after the diagnosis of malignant tumor and pathological reports of such specimens shall also be provided"}
• {"criterion_text":"-The following conditions must be met in terms of the time of the first administration of the investigational product: at least 3 weeks (or 5 half-lives of the drug, whichever is shorter) from the previous major surgery, medical device treatment, locoregional radiotherapy (except for palliative radiotherapy for bone lesions), cytotoxic chemotherapy, immunotherapy, or biological product therapy; at least 2 weeks from the previous hormone therapy or small molecular targeted therapy; at least 1 week from the administration of the traditional Chinese medicine for anti-cancer indications or minor surgery; and recovery of treatment-induced AEs to Grade ≤ 1 (CTCAE v5.0, except for peripheral neurotoxicity and alopecia)"}
• {"criterion_text":"-ECOG PS score of 0-1 within 1 week prior to randomization"}
• {"criterion_text":"-Life expectancy > 3 months"}
• {"criterion_text":"-Adequate organ functions as confirmed by laboratory tests within 1 week prior to randomization (no blood transfusions or treatment with granulocyte colony-stimulating factor is allowed within 14 days prior to the first dose"}

Exclusion criteria

• {"criterion_text":"-Histologically or cytologically confirmed tumor containing components of small cell lung cancer, neuroendocrine carcinoma, or sarcomatoid carcinoma"}
• {"criterion_text":"-Patients with active systemic infectious diseases requiring intravenous antibiotics within 2 weeks prior to randomization"}
• {"criterion_text":"-Patients who have used moderate or potent CYP2D6 or CYP3A inhibitors or inducers within 2 weeks prior to randomization"}
• {"criterion_text":"-Patients who have received systemic corticosteroids (prednisone > 10 mg/d or equivalent dose of similar drug) or other immunosuppressants within 2 weeks prior to randomization; Except: patients treated with topical, ocular, intra-articular, intranasal, and inhaled corticosteroids; short-term prophylactic use of corticosteroids for contrast agents, etc"}
• {"criterion_text":"-Patients with known active or suspected autoimmune diseases. Patients with autoimmune-related hypothyroidism and receiving thyroid hormone replacement therapy and those with type 1 diabetes mellitus controlled with insulin therapy are eligible to be enrolled"}
• {"criterion_text":"-Patients who have received live vaccine or live attenuated vaccine within 4 weeks prior to randomization"}
• {"criterion_text":"-Patients who are known to have anaphylaxis to macromolecular protein preparations/monoclonal antibodies or are allergic to any component in the formulation of the investigational product"}
• {"criterion_text":"-Patients with active tuberculosis"}
• {"criterion_text":"-Patients with a history of immunodeficiency, including human immunodeficiency virus (HIV)-positive or other acquired or congenital immunodeficiencies, or history of organ transplantation"}
• {"criterion_text":"-Patients with active HBV or HCV infection or HBV/HCV co-infection; Note: Patients who test positive for HBsAg or HBcAb during screening must further undergo HBV-DNA testing. If the test result suggests < 500 IU/mL, < 2500 copies/mL, or < ULN, the patient can be enrolled. Patients with HBV-DNA detected must agree to receive treatment with anti-HBV nucleos(t)ide analogues during the study. Patients who test positive for HCV antibody must further undergo HCV-RNA testing. If the test result suggests < ULN, the patient can be enrolled. Patients with HBV/HCV co-infection (positive for HBsAg or HBcAb and positive for HCV antibody) must be excluded"}
• {"criterion_text":"-Pregnant or lactating women"}
• {"criterion_text":"-Prior treatment with any medication targeting topoisomerase I, including chemotherapy or ADCs"}
• {"criterion_text":"-Patients who are not suitable for participating in this clinical study due to any clinical or laboratory abnormalities or other reasons as assessed by the investigator"}
• {"criterion_text":"-Radical radiation therapy within 3 months prior to the first dose"}
• {"criterion_text":"-History of any second malignancy within 2 years prior to randomization, except for early-stage malignancies (carcinoma in situ or stage I tumors) that have received radical treatment, such as non-melanoma skin cancer, cervical carcinoma in situ, localized prostate cancer, ductal carcinoma in situ of the breast, and papillary thyroid carcinoma"}
• {"criterion_text":"-History of adverse events leading to permanent discontinuation of immunotherapy, or occurrence of ≥ Grade 2 immune-related pneumonitis or myocarditis during prior immunotherapy"}
• {"criterion_text":"-Presence of uncontrollable pleural effusion, pericardial effusion, or ascites requiring repeated drainage"}
• {"criterion_text":"-Presence of spinal cord compression or clinically active metastases to central nervous system (referring to untreated or symptomatic metastases, or metastases requiring corticosteroids or anticonvulsants to control associated symptoms), carcinomatous meningitis. Subjects who have previously received treatment for brain metastases (such as whole brain radiotherapy or stereotactic brain radiotherapy) may be eligible, provided that they are clinically stable for at least 4 weeks with no imaging evidence of brain metastasis progression"}
• {"criterion_text":"-Subjects with current or prior history of clinically significant pulmonary impairment due to pulmonary comorbidities, including but not limited to: any underlying lung disease (e.g., pulmonary embolism within 3 months prior to the first dose, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, interstitial pneumonia, pneumoconiosis, drug-related pneumonitis, and pleural effusion), any autoimmune, connective tissue, or inflammatory disease that may involve the lungs (i.e., rheumatoid arthritis, Sjogren's syndrome, sarcoidosis), prior pneumonectomy that may interfere with the detection and management of suspected drug-related pulmonary toxicity, or history of radiation pneumonitis within 6 months"}
• {"criterion_text":"-Patients with any poorly-controlled cardiovascular and cerebrovascular clinical symptoms or diseases, including but not limited to: (1) NYHA Class II or greater heart failure or left ventricular ejection fraction (LVEF) < 50%; (2) unstable angina pectoris; (3) myocardial infarction or cerebrovascular accident within 6 months (except lacunar infarction, slight cerebral ischemia, or transient ischemic attack); (4) poorly controlled arrhythmia (including QTc intervals ≥ 470 ms) (QTc intervals are calculated by Fridericia's formula); (5) poorly-controlled hypertension (systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg after active treatment)"}

Primary endpoints

• {"endpoint_text":"-Objective response rate (ORR) (assessed by the Blinded Independent Central Review [BICR] as per RECIST v1.1)","definition_or_measurement_approach":"Assessed by the Blinded Independent Central Review (BICR) according to RECIST v1.1"}

Secondary endpoints

• {"endpoint_text":"-Overall survival (OS)","definition_or_measurement_approach":""}
• {"endpoint_text":"-Duration of response (DOR) and disease control rate (DCR) (assessed by the BICR and the investigator)","definition_or_measurement_approach":"Assessed by the Blinded Independent Central Review (BICR) and the investigator"}
• {"endpoint_text":"-Adverse events (AEs), serious adverse events (SAEs), laboratory tests, vital signs, 12-lead ECG, and physical examination","definition_or_measurement_approach":"Safety assessments include recording AEs/SAEs, laboratory tests, vital signs, 12-lead ECG and physical examinations"}
• {"endpoint_text":"-Blood drug concentration and pharmacokinetics parameters of HLX43 at different doses (ADC, total antibody, and free small molecule toxin)","definition_or_measurement_approach":"Measurement of blood drug concentration and PK parameters for ADC, total antibody and free small molecule toxin at different dose levels"}
• {"endpoint_text":"-Positive rates of anti-HLX43 antibody (ADA) and neutralizing antibody (NAb)","definition_or_measurement_approach":"Assessment of immunogenicity: rates of ADA and neutralizing antibodies"}
• {"endpoint_text":"-Potential predictive or drug resistance biomarkers, such as PD-L1 expression levels, tumor-related gene mutations or expression levels, serum proteomic profiles","definition_or_measurement_approach":"Exploratory biomarker analyses including PD-L1 expression, tumor gene mutations/expression levels and serum proteomics"}
• {"endpoint_text":"-Quality of life assessment","definition_or_measurement_approach":""}
• {"endpoint_text":"-Objective response rate (ORR) (assessed by investigator as per RECIST v1.1)","definition_or_measurement_approach":"Assessed by investigator using RECIST v1.1"}
• {"endpoint_text":"-Progression-free survival (PFS) (assessed by the BICR and the investigator as per RECIST v1.1)","definition_or_measurement_approach":"Assessed by the Blinded Independent Central Review (BICR) and the investigator using RECIST v1.1"}

Italy

Earliest CTIS Part Ii Submission Date

11-12-2025

Latest Decision Or Authorization Date

15-05-2026

Processing Time Days

155

Number Of Sites

4

Number Of Participants

11

Romania

Earliest CTIS Part Ii Submission Date

23-02-2026

Latest Decision Or Authorization Date

01-04-2026

Processing Time Days

37

Number Of Sites

5

Number Of Participants

3

Poland

Earliest CTIS Part Ii Submission Date

06-03-2026

Latest Decision Or Authorization Date

15-05-2026

Processing Time Days

70

Number Of Sites

2

Number Of Participants

3

Spain

Earliest CTIS Part Ii Submission Date

08-01-2026

Latest Decision Or Authorization Date

15-05-2026

Processing Time Days

127

Number Of Sites

8

Number Of Participants

13

France

Earliest CTIS Part Ii Submission Date

20-01-2026

Latest Decision Or Authorization Date

15-05-2026

Processing Time Days

115

Number Of Sites

3

Number Of Participants

11

Primary sponsor

Full Name

Shanghai Henlius Biotech Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

China

Contract research organisations

Name

Almac Clinical Technologies LLC

Responsibilities

code:3

Name

Fisher Clinical Services GmbH

Responsibilities

code:14

Name

Medidata Solutions Inc.

Responsibilities

code:7

Name

Veeva Systems Inc.

Responsibilities

code:7

Third parties

• {"country":"China","full_name":"Guangzhou Burning Rock Dx Co. Ltd.","duties_or_roles":"code:4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"code:7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"China","full_name":"Calyx China Co. Ltd.","duties_or_roles":"central Imaging","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Netherlands","full_name":"Eurofins Central Laboratory B.V.","duties_or_roles":"Samples storage service","organisation_type":"Pharmaceutical company"}
• {"country":"China","full_name":"Teddy Clinical Research Laboratory (Wuxi) Ltd.","duties_or_roles":"code:4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Veeva Systems Inc.","duties_or_roles":"code:7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"China","full_name":"Shanghai Henlius Biologics Co. Ltd.","duties_or_roles":"code:4","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Fisher Clinical Services GmbH","duties_or_roles":"code:14","organisation_type":"Pharmaceutical company"}
• {"country":"Israel","full_name":"Oncohost Ltd.","duties_or_roles":"code:4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Almac Clinical Technologies LLC","duties_or_roles":"code:3","organisation_type":"Pharmaceutical company"}